Retinoic acid affects craniofacial patterning by changing Fgf8 expression in the pharyngeal ectoderm

Retinoic acid signaling plays important roles in establishing normal patterning and cellular differentiation during embryonic development. In this study, we show that single administration of retinoic acid at embryonic day 8.5 causes homeotic transformation of the lower jaw into upper jaw-like structures. This homeosis was preceded by downregulation of Fgf8 and Sprouty expression in the proximal domain of the first pharyngeal arch. Downregulation of mesenchymal genes such as Dlx5, Hand2, Tbx1 and Pitx2 was also observed. The oropharynx in retinoic acid-treated embryos was severely constricted. Consistent with this observation, Patched expression in the arch endoderm and mesenchyme was downregulated. Thus, retinoic acid affects the expression of subsets of epithelial and mesenchymal genes, possibly disrupting the regional identity of the pharyngeal arch.     

TGF-β1 and serum both stimulate contraction but differentially affect apoptosis in 3D collagen gels

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-β1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen gels. Human fetal lung fibroblasts were cultured in floating type I collagen gels, exposed to TGF-β1 or FCS, and allowed to contract for 5 days. Apoptosis was evaluated using TUNEL and confirmed by DNA content profiling. Both TGF-β1 and serum significantly augmented collagen gel contraction. TGF-β1 also increased apoptosis assessed by TUNEL positivity and DNA content analysis. In contrast, serum did not affect apoptosis. TGF-β1 induction of apoptosis was associated with augmented expression of Bax, a pro-apoptotic member of the Bax/Bcl-2 family, inhibition of Bcl-2, an anti-apoptotic member of the same family, and inhibition of both cIAP-1 and XIAP, two inhibitors of the caspase cascade. Serum was associated with an increase in cIAP-1 and Bcl-2, anti-apoptotic proteins. Interestingly, serum was also associated with an apparent increase in Bax, a pro-apoptotic protein. Blockade of Smad3 with either siRNA or by using murine fibroblasts deficient in Smad3 resulted in a lack of TGF-β induction of augmented contraction and apoptosis. Contraction induced by different factors, therefore, may be differentially associated with apoptosis, which may be related to the persistence or resolution of the fibroblasts that accumulate following injury.     

Recognition of 3D flexible objects by GRBF

Recently Poggio and Edelman have shown that for each object there exists a smooth mapping from an arbitrary view to its standard view and that the mapping can be learned from a sparse data set. In this paper, we extend their scheme further to deal with 3D flexible objects. We show the mappings from an arbitrary view to the standard view, and its rotated view can be synthesized even for a flexible object by learning from examples. To classify 3D flexible objects, we propose two methods, which do not require any special knowledge on the target flexible objects. They are: (1) learning the characteristic function of the object and (2) learning the view-change transformation. We show their performance by computer simulations. Received: 1 March 1993/Accepted in revised form: 7 June 1993     

New ENU-induced semidominant mutation, Ali18, causes inflammatory arthritis, dermatitis, and osteoporosis in the mouse

Inflammation is a complex cellular and humoral response against trauma and infection, and its presence leads to destruction of tissue in humans. The mechanisms that initiate inflammatory diseases remain largely unknown because of complex interactions between multiple genetic and environmental factors during pathogenesis. Animal models for human diseases offer dissection of complex pathogenesis by inbred genetic backgrounds and controlled circumstances. In this article we report a chemically induced new mutation, Ali18 (Abnormal limb), as a mouse model for inflammatory arthritis and dermatitis. Ali18/+ mice exhibit rubor and swelling of footpads in hindlimbs in adults. In Ali18/Ali18 mice, the digits in forelimbs and hindlimbs and tails were necrotic and/or deformed by severe swelling. Histologic analysis revealed infiltration of mixed populations of inflammatory cells into bone marrow, peripheral joints, and skin in the affected areas of Ali18/Ali18 mice. In addition, generalized osteoporosis-like phenotypes were confirmed by dual energy X-ray absorptiometry (DXA), microcomputed tomography (μCT), and peripheral quantitative computed tomography (pQCT) in homozygous animals. Whereas the Ali18 mutation was mapped to a single locus, the phenotype presentation was altered by complex modifier effects from other inbred genetic backgrounds. Detailed analysis of the Ali18 phenotype and identification of the mutation and its modifier genes may provide molecular insights into the complex nature of inflammatory diseases and the relationship between inflammation and bone metabolism.     

Comparison of biological activities of endothelin-1, -2 and -3 in murine and human fibroblast cell lines

The effects of three forms of endothelin (ET), ET-1, -2 and -3, on intracellular free Ca2+ concentration ([Ca2+]i) and their receptor binding activities have been compared in murine fibroblast cell line Swiss 3T3 as well as diploid human fibroblast cell line FS-4. In both cell lines, ET-1 and -2 induced a profound increase in [Ca2+]i with a similar dose-response relationship; ET-3 was far less potent. ET-1 and -2 showed specific binding to both cell lines with similar dissociation constants and numbers of binding sites. Negligible specific binding of ET-3 was detected. These findings indicate that these two fibroblast populations possess high affinity receptors for ET-1 and -2 and practically no ET-3 receptors for ET-3, and binding of ET-1 and -2 increases [Ca2+]i in these cell lines.     

Peptide ligand screening of α-synuclein aggregation modulators by <Emphasis Type="Italic">in silico</Emphasis> panning

Background  

α-Synuclein is a Parkinson's-disease-related protein. It forms aggregates in vivo, and these aggregates cause cell cytotoxicity. Aggregation inhibitors are expected to reduce α-synuclein cytotoxicity, and an aggregation accelerator has recently been reported to reduce α-synuclein cytotoxicity. Therefore, amyloid aggregation modulating ligands are expected to serve as therapeutic medicines.     

Winner and loser effects of juvenile cricket Gryllus bimaculatus

Journal of Ethology - Agonistic encounters of juvenile male crickets were analyzed behaviourally. In a pairing between adult and juvenile male crickets, the juvenile crickets were usually beaten by...